Prospective analysis of circulating metabolites and endometrial cancer risk

Laure Dossus; Eirini Kouloura; Carine Biessy; Vivian Viallon; Alexandros P. Siskos; Niki Dimou; Sabina Rinaldi; Melissa A. Merritt; Naomi Allen; Renee Fortner; Rudolf Kaaks; Elisabete Weiderpass; Inger T. Gram; Joseph A. Rothwell; Lucie Lécuyer; Gianluca Severi; Matthias B. Schulze; Therese Haugdahl Nøst; Marta Crous-Bou; Maria Jose Sánchez; Pilar Amiano; Sandra M. Colorado-Yohar; Aurelio Barricarte Gurrea; Julie A. Schmidt; Domenico Palli; Claudia Agnoli; Rosario Tumino; Carlotta Sacerdote; Amalia Mattiello; Roel Vermeulen; Alicia K. Heath; Sofia Christakoudi; Konstantinos K. Tsilidis; Ruth C. Travis; Marc J. Gunter; Hector C. Keun

doi:10.1016/j.ygyno.2021.06.001

Prospective analysis of circulating metabolites and endometrial cancer risk

Laure Dossus
, Eirini Kouloura
, Carine Biessy
, Vivian Viallon
, Alexandros P. Siskos
, Niki Dimou
, Sabina Rinaldi
, Melissa A. Merritt
, Naomi Allen
, Renee Fortner
, Rudolf Kaaks
, Elisabete Weiderpass
, Inger T. Gram
, Joseph A. Rothwell
, Lucie Lécuyer
, Gianluca Severi
, Matthias B. Schulze
, Therese Haugdahl Nøst
, Marta Crous-Bou
, Maria Jose Sánchez

Pilar Amiano, Sandra M. Colorado-Yohar, Aurelio Barricarte Gurrea, Julie A. Schmidt, Domenico Palli, Claudia Agnoli, Rosario Tumino, Carlotta Sacerdote, Amalia Mattiello, Roel Vermeulen, Alicia K. Heath, Sofia Christakoudi, Konstantinos K. Tsilidis, Ruth C. Travis, Marc J. Gunter, Hector C. Keun

Research output: Contribution to journal › Article › peer-review

Abstract

Background: Endometrial cancer is strongly associated with obesity and dysregulation of metabolic factors such as estrogen and insulin signaling are causal risk factors for this malignancy. To identify additional novel metabolic pathways associated with endometrial cancer we performed metabolomic analyses on pre-diagnostic plasma samples from 853 case-control pairs from the European Prospective Investigation into Cancer and Nutrition (EPIC). Methods: A total of 129 metabolites (acylcarnitines, amino acids, biogenic amines, glycerophospholipids, hexoses, and sphingolipids) were measured by liquid chromatography-mass spectrometry. Conditional logistic regression estimated the associations of metabolites with endometrial cancer risk. An analysis focusing on clusters of metabolites using the bootstrap lasso method was also employed. Results: After adjustment for body mass index, sphingomyelin [SM] C18:0 was positively (OR_1SD: 1.18, 95% CI: 1.05–1.33), and glycine, serine, and free carnitine (C0) were inversely (OR_1SD: 0.89, 95% CI: 0.80–0.99; OR_1SD: 0.89, 95% CI: 0.79–1.00 and OR_1SD: 0.91, 95% CI: 0.81–1.00, respectively) associated with endometrial cancer risk. Serine, C0 and two sphingomyelins were selected by the lasso method in >90% of the bootstrap samples. The ratio of esterified to free carnitine (OR_1SD: 1.14, 95% CI: 1.02–1.28) and that of short chain to free acylcarnitines (OR_1SD: 1.12, 95% CI: 1.00–1.25) were positively associated with endometrial cancer risk. Further adjustment for C-peptide or other endometrial cancer risk factors only minimally altered the results. Conclusion: These findings suggest that variation in levels of glycine, serine, SM C18:0 and free carnitine may represent specific pathways linked to endometrial cancer development. If causal, these pathways may offer novel targets for endometrial cancer prevention.

Original language	English
Pages (from-to)	475-481
Number of pages	7
Journal	Gynecologic Oncology
Volume	162
Issue number	2
DOIs	https://doi.org/10.1016/j.ygyno.2021.06.001
Publication status	Published - Aug 2021
Externally published	Yes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Amino acids
Endometrial cancer
Lipids
Metabolomics
Obesity

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10.1016/j.ygyno.2021.06.001

Cite this

Dossus, L., Kouloura, E., Biessy, C., Viallon, V., Siskos, A. P., Dimou, N., Rinaldi, S., Merritt, M. A., Allen, N., Fortner, R., Kaaks, R., Weiderpass, E., Gram, I. T., Rothwell, J. A., Lécuyer, L., Severi, G., Schulze, M. B., Nøst, T. H., Crous-Bou, M., ... Keun, H. C. (2021). Prospective analysis of circulating metabolites and endometrial cancer risk. Gynecologic Oncology, 162(2), 475-481. https://doi.org/10.1016/j.ygyno.2021.06.001

@article{e31a9e1bc0474e698745f71473fc46e4,

title = "Prospective analysis of circulating metabolites and endometrial cancer risk",

abstract = "Background: Endometrial cancer is strongly associated with obesity and dysregulation of metabolic factors such as estrogen and insulin signaling are causal risk factors for this malignancy. To identify additional novel metabolic pathways associated with endometrial cancer we performed metabolomic analyses on pre-diagnostic plasma samples from 853 case-control pairs from the European Prospective Investigation into Cancer and Nutrition (EPIC). Methods: A total of 129 metabolites (acylcarnitines, amino acids, biogenic amines, glycerophospholipids, hexoses, and sphingolipids) were measured by liquid chromatography-mass spectrometry. Conditional logistic regression estimated the associations of metabolites with endometrial cancer risk. An analysis focusing on clusters of metabolites using the bootstrap lasso method was also employed. Results: After adjustment for body mass index, sphingomyelin [SM] C18:0 was positively (OR1SD: 1.18, 95\% CI: 1.05–1.33), and glycine, serine, and free carnitine (C0) were inversely (OR1SD: 0.89, 95\% CI: 0.80–0.99; OR1SD: 0.89, 95\% CI: 0.79–1.00 and OR1SD: 0.91, 95\% CI: 0.81–1.00, respectively) associated with endometrial cancer risk. Serine, C0 and two sphingomyelins were selected by the lasso method in >90\% of the bootstrap samples. The ratio of esterified to free carnitine (OR1SD: 1.14, 95\% CI: 1.02–1.28) and that of short chain to free acylcarnitines (OR1SD: 1.12, 95\% CI: 1.00–1.25) were positively associated with endometrial cancer risk. Further adjustment for C-peptide or other endometrial cancer risk factors only minimally altered the results. Conclusion: These findings suggest that variation in levels of glycine, serine, SM C18:0 and free carnitine may represent specific pathways linked to endometrial cancer development. If causal, these pathways may offer novel targets for endometrial cancer prevention.",

keywords = "Amino acids, Endometrial cancer, Lipids, Metabolomics, Obesity",

author = "Laure Dossus and Eirini Kouloura and Carine Biessy and Vivian Viallon and Siskos, \{Alexandros P.\} and Niki Dimou and Sabina Rinaldi and Merritt, \{Melissa A.\} and Naomi Allen and Renee Fortner and Rudolf Kaaks and Elisabete Weiderpass and Gram, \{Inger T.\} and Rothwell, \{Joseph A.\} and Lucie L{\'e}cuyer and Gianluca Severi and Schulze, \{Matthias B.\} and N{\o}st, \{Therese Haugdahl\} and Marta Crous-Bou and S{\'a}nchez, \{Maria Jose\} and Pilar Amiano and Colorado-Yohar, \{Sandra M.\} and Gurrea, \{Aurelio Barricarte\} and Schmidt, \{Julie A.\} and Domenico Palli and Claudia Agnoli and Rosario Tumino and Carlotta Sacerdote and Amalia Mattiello and Roel Vermeulen and Heath, \{Alicia K.\} and Sofia Christakoudi and Tsilidis, \{Konstantinos K.\} and Travis, \{Ruth C.\} and Gunter, \{Marc J.\} and Keun, \{Hector C.\}",

note = "Publisher Copyright: {\textcopyright} 2021",

year = "2021",

month = aug,

doi = "10.1016/j.ygyno.2021.06.001",

language = "English",

volume = "162",

pages = "475--481",

journal = "Gynecologic Oncology",

issn = "0090-8258",

publisher = "Academic Press Inc.",

number = "2",

}

Dossus, L, Kouloura, E, Biessy, C, Viallon, V, Siskos, AP, Dimou, N, Rinaldi, S, Merritt, MA, Allen, N, Fortner, R, Kaaks, R, Weiderpass, E, Gram, IT, Rothwell, JA, Lécuyer, L, Severi, G, Schulze, MB, Nøst, TH, Crous-Bou, M, Sánchez, MJ, Amiano, P, Colorado-Yohar, SM, Gurrea, AB, Schmidt, JA, Palli, D, Agnoli, C, Tumino, R, Sacerdote, C, Mattiello, A, Vermeulen, R, Heath, AK, Christakoudi, S, Tsilidis, KK, Travis, RC, Gunter, MJ & Keun, HC 2021, 'Prospective analysis of circulating metabolites and endometrial cancer risk', Gynecologic Oncology, vol. 162, no. 2, pp. 475-481. https://doi.org/10.1016/j.ygyno.2021.06.001

TY - JOUR

T1 - Prospective analysis of circulating metabolites and endometrial cancer risk

AU - Dossus, Laure

AU - Kouloura, Eirini

AU - Biessy, Carine

AU - Viallon, Vivian

AU - Siskos, Alexandros P.

AU - Dimou, Niki

AU - Rinaldi, Sabina

AU - Merritt, Melissa A.

AU - Allen, Naomi

AU - Fortner, Renee

AU - Kaaks, Rudolf

AU - Weiderpass, Elisabete

AU - Gram, Inger T.

AU - Rothwell, Joseph A.

AU - Lécuyer, Lucie

AU - Severi, Gianluca

AU - Schulze, Matthias B.

AU - Nøst, Therese Haugdahl

AU - Crous-Bou, Marta

AU - Sánchez, Maria Jose

AU - Amiano, Pilar

AU - Colorado-Yohar, Sandra M.

AU - Gurrea, Aurelio Barricarte

AU - Schmidt, Julie A.

AU - Palli, Domenico

AU - Agnoli, Claudia

AU - Tumino, Rosario

AU - Sacerdote, Carlotta

AU - Mattiello, Amalia

AU - Vermeulen, Roel

AU - Heath, Alicia K.

AU - Christakoudi, Sofia

AU - Tsilidis, Konstantinos K.

AU - Travis, Ruth C.

AU - Gunter, Marc J.

AU - Keun, Hector C.

PY - 2021/8

Y1 - 2021/8

N2 - Background: Endometrial cancer is strongly associated with obesity and dysregulation of metabolic factors such as estrogen and insulin signaling are causal risk factors for this malignancy. To identify additional novel metabolic pathways associated with endometrial cancer we performed metabolomic analyses on pre-diagnostic plasma samples from 853 case-control pairs from the European Prospective Investigation into Cancer and Nutrition (EPIC). Methods: A total of 129 metabolites (acylcarnitines, amino acids, biogenic amines, glycerophospholipids, hexoses, and sphingolipids) were measured by liquid chromatography-mass spectrometry. Conditional logistic regression estimated the associations of metabolites with endometrial cancer risk. An analysis focusing on clusters of metabolites using the bootstrap lasso method was also employed. Results: After adjustment for body mass index, sphingomyelin [SM] C18:0 was positively (OR1SD: 1.18, 95% CI: 1.05–1.33), and glycine, serine, and free carnitine (C0) were inversely (OR1SD: 0.89, 95% CI: 0.80–0.99; OR1SD: 0.89, 95% CI: 0.79–1.00 and OR1SD: 0.91, 95% CI: 0.81–1.00, respectively) associated with endometrial cancer risk. Serine, C0 and two sphingomyelins were selected by the lasso method in >90% of the bootstrap samples. The ratio of esterified to free carnitine (OR1SD: 1.14, 95% CI: 1.02–1.28) and that of short chain to free acylcarnitines (OR1SD: 1.12, 95% CI: 1.00–1.25) were positively associated with endometrial cancer risk. Further adjustment for C-peptide or other endometrial cancer risk factors only minimally altered the results. Conclusion: These findings suggest that variation in levels of glycine, serine, SM C18:0 and free carnitine may represent specific pathways linked to endometrial cancer development. If causal, these pathways may offer novel targets for endometrial cancer prevention.

AB - Background: Endometrial cancer is strongly associated with obesity and dysregulation of metabolic factors such as estrogen and insulin signaling are causal risk factors for this malignancy. To identify additional novel metabolic pathways associated with endometrial cancer we performed metabolomic analyses on pre-diagnostic plasma samples from 853 case-control pairs from the European Prospective Investigation into Cancer and Nutrition (EPIC). Methods: A total of 129 metabolites (acylcarnitines, amino acids, biogenic amines, glycerophospholipids, hexoses, and sphingolipids) were measured by liquid chromatography-mass spectrometry. Conditional logistic regression estimated the associations of metabolites with endometrial cancer risk. An analysis focusing on clusters of metabolites using the bootstrap lasso method was also employed. Results: After adjustment for body mass index, sphingomyelin [SM] C18:0 was positively (OR1SD: 1.18, 95% CI: 1.05–1.33), and glycine, serine, and free carnitine (C0) were inversely (OR1SD: 0.89, 95% CI: 0.80–0.99; OR1SD: 0.89, 95% CI: 0.79–1.00 and OR1SD: 0.91, 95% CI: 0.81–1.00, respectively) associated with endometrial cancer risk. Serine, C0 and two sphingomyelins were selected by the lasso method in >90% of the bootstrap samples. The ratio of esterified to free carnitine (OR1SD: 1.14, 95% CI: 1.02–1.28) and that of short chain to free acylcarnitines (OR1SD: 1.12, 95% CI: 1.00–1.25) were positively associated with endometrial cancer risk. Further adjustment for C-peptide or other endometrial cancer risk factors only minimally altered the results. Conclusion: These findings suggest that variation in levels of glycine, serine, SM C18:0 and free carnitine may represent specific pathways linked to endometrial cancer development. If causal, these pathways may offer novel targets for endometrial cancer prevention.

KW - Amino acids

KW - Endometrial cancer

KW - Lipids

KW - Metabolomics

KW - Obesity

UR - https://www.scopus.com/pages/publications/85107389683

U2 - 10.1016/j.ygyno.2021.06.001

DO - 10.1016/j.ygyno.2021.06.001

M3 - Article

SN - 0090-8258

VL - 162

SP - 475

EP - 481

JO - Gynecologic Oncology

JF - Gynecologic Oncology

IS - 2

ER -

Prospective analysis of circulating metabolites and endometrial cancer risk

Abstract

UN SDGs

Keywords

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